Cellular and Metabolic Engineering
132 Mugar Hall
Plants are an important source of small molecule drugs or pharmaceuticals (pictured is the Madagascar rosy periwinkle plant). The biodiversity found in unique environments such as the rain forests contain a wealth of potentially powerful drugs for the treatment of critical diseases such as infections, cancer, and AIDs. The availability of the plant may limit the supply of important plant- derived pharmaceuticals.
Cell cultures of plants can provide an alternative source of plant-derived drugs. Our vision is to meet and supply the need of these plant-derived drugs by producing the medicinal compounds in cell cultures rather than extracting them from the whole plant. Plant cell cultures can be grown in 125 or 250 mL Erlenmeyer flasks as shown here. These small-scale systems allow the study of a variety of parameters affecting growth and production (i.e. nutrient composition, inducer compounds, temperature, pH, dissolved gas composition).
Cells are micro-bioreactors housing enzymes (biological catalysts) that catalyze a network of reactions leading to the desired products. Single plant cells are approximately 20 µm in diameter but generally plant cells grow as aggregates ranging in size from 100 – 1000 µm. The plant cells shown here have been treated with a viability stain (fluorescein diacetate); living or viable cells will fluoresce green under UV light.
Once growth and production of the plant-derived drug has been optimized in the flasks, cells are cultured in a larger scale system such as this bench-top bioreactor (2 L bioreactor pictured) for further process development. Large-scale bioreactors (10 – 10,000 L) are necessary for producing large quantities of these plant-derived drugs. The bioreactor system also allows for the control of parameters affecting growth and production such as pH, temperature, dissolved gas composition, and nutrient concentrations. Once made by the cells, the product is harvested or recovered from the cells, isolated and separated from other compounds made by the cells, and finally purified.
The chemical structure of vincristine and vinblastine, produced by the Madagascar periwinkle, is shown here. These two small molecule drugs are used in the treatment of cancers and are currently marketed by Eli Lilly and other companies. Vinblastine sulfate (tradename Velbane and Velsar) costs ~$2/mg or $2 million/kg and is used in the treatment of testicular cancer, various lymphomas particularly Hodgkin’s disease, and Kaposi’s sarcoma. Vincristine sulfate (tradename Oncovin and Vincasar PFS) costs ~$15/mg or $15 million/kg and is presently the treatment of choice in childhood leukemia. Both of these drugs prevent the multiplication of cancer cells by binding to tubulin and blocking the polymerization to form microtubules required for cell division. (Drug prices from Redbook 2002)